Studies are continuing on the mechanism by which infusion of donor antigen (in the form of bone marrow) produces specific increased survival of tissue allografts in immunosuppressed hosts (treated with antilymphocyte serum). The preliminary results with anti-bone marrow serum will be extended, with particular attention given to variation of the time AMS is given and its effect in pre-sensitized animals. The effect of AMS on the unresponsiveness associated with chimerism will especially be studied. The mechanism by which cytoxan exerts its effect will be studied in regard to whether its action is on donor or host cells. Marrow from cytoxan treated donors will be tested for its ability to prolong grafts in ALS-treated mice. A major experimental effort will be performed to see if active enhancement can be achieved in the pre-sensitized animal after sensitization with the weak antigenic stimulus of blood. Pre-sensitized mice will be treated with inhibitors of humoral response (cytoxan, AMS) for varying and prolonged periods prior to treatment with ALS and marrow. The experiments to prolong canine renal allografts with ALS and donor bone marrow in recipients receiving steroids and Imuran will be initiated. BIBLIOGRAPHIC REFERENCES: Monaco, A.P. What's new in surgery: Transplantation. Surg., Gyn. and Obst. 140:215, 1975. Hirsh, M.S., Ellis, D.A., Kelly, Ann P., Proffitt, M.R., Black, P.H., Monaco, A.P., and Wood, Mary L. Activation of C-Type viruses during skin graft rejection in the mouse. Interrelationships between immunostimulation and immunosuppression. International Journal of Cancer 15:493-502, 1975.